This invention is in the field of antiviral agents and specifically relates to compounds, compositions and methods for treating herpes-related disorders.
There is a great need for new therapies for the treatment of viral diseases. Whereas there has been great progress in developing a variety of therapies for the treatment of bacterial infections, there are few viable therapies for the treatment of viruses. Zidovudine is the primary approved treatment for human immunodeficiency virus. Ganciclovir, acyclovir and foscarnet are currently utilized for the treatment of herpesvirus infections. However, these therapies can have substantial side effects based on their deleterious effects on host cell DNA replication or their effect on a limited number of viral infections. In addition, viruses are known to develop resistance to therapies, which causes a progressive decline in efficacy.
Viruses are classified into broad categories based on whether they incorporate RNA or DNA. Important virus families classified of the DNA type include adenoviridae, poxviridae, papovaviridae and herpesviridae.
Herpesviridae is a family of DNA viruses which include herpes simplex virus type-1 (HSV-1), herpes simplex virus type-2 (HSV-2), cytomegalovirus (CMV), varicella-zoster virus (VZV), Epstein-Barr virus, human herpesvirus-6 (HHV6), human herpesvirus-7 (HHV7), human herpesvirus-8 (HHV8), pseudorabies and rhinotracheitis, among others.
It is known that herpesviruses express their genetic content by directing the synthesis of a number of proteins encoded by the herpesvirus DNA in the host cell. One of the important virus-encoded proteins is made as a precursor consisting of an amino terminal-located protease and carboxyl terminal-located assembly protein. This precursor is proteolytically processed in an autocatalytic manner at a specific amino acid sequence known as the xe2x80x9creleasexe2x80x9d site yielding separate protease and assembly protein. The assembly protein is cleaved further by the protease at another specific amino acid sequence known as the xe2x80x9cmaturationxe2x80x9d cleavage site. Recently, EP No. 514,830, published Nov. 25, 1992, describes a virus-specific serine protease which has a role in herpesvirus replication. Additionally, Lui and Roizman [J. Virol, 65, 5149 (1991)] describe the sequence and activity of a protease and the associated assembly protein encoded by UL26 of HSV-1. A. R. Welch et al. [Proc. Natl. Acad. Sci. USA, 88, 10792 (1991) and WO93/01291, published Jan. 21, 1993] describe the related protease (also known as assemblin) and assembly protein encoded by UL80 of CMV. An approach currently being investigated for potential use in the treatment of herpesvirus infections is the development of inhibitors of herpesvirus proteases.
4H-3,1-Benzoxazinones have been described in the literature as having serine protease activity, among others. While compounds of this type have been reported to have serine protease inhibitory activity, none have been reported to inhibit viral assemblin protease. For example Teshima et al. [J. Biol. Chem., 257, 5085-5091 (1982)] describe various 2-alkyl-4H-3,1-benzoxazin-4-ones as enzyme inhibitors. Moorman and Abeles [J. Amer. Chem. Soc., 104, 6785-6786 (1982)] describe 4H-3,1-benzoxazin-2,4-dione as having some enzyme inhibitory activity. R. Stein, et al. [Biochemistry, 26, 4126-4130, (1987)] describe 2-alkyl-4H-benzoxazin-4-ones, with further substitution at the 5, 6 and 7 positions, as inhibiting the elastase enzyme. WO publication 92/18488 (published Oct. 29, 1992) describes 2-alkyl-4H-3,1-benzoxazin-4-ones with substitution at the 5 and 7 positions as selective inhibitors of elastase. European Application 206,323 (published Dec. 30, 1985) describes 2-alkoxy- and 2-aryloxy- and 2-aralkoxy-4H-3,1-benzoxazin-4-ones, having substitution at the 5, 6, 7, and 8 positions, as enzyme inhibitors. U.S. Pat. No. 4,1745,116, to A. Kranz et al. describes 2-alkoxy, 2-aryloxy- and 2-aralkoxy-4H-3,1-benzoxazin-4-ones, having further substitution at the 5, 7 and 8 positions, as enzyme inhibitors. U.S. Pat. No. 5,428,021, to C. Hiebert et al., describes 6-(aminoacid)amino-2-alkoxybenzoxazinones as elastase inhibitors. WO publication 96/07648, published Mar. 14, 1996, describes 2-phenylamino-benzoxazinones for the treatment of Alzheimer""s, and specifically, 6-chloro-2-(2-iodophenylamino)-benzo [d][1,3]oxazin-4-one is described.
2-Amino-4H-3,1-benzoxazinones have been described. A. Krantz et al. [J. Med. Chem., 33, 464-479 (1990)] describe 4H-3,1-benzoxazin-4-ones substituted with alkyl, alkylamino, alkoxy and alkylthio substituents at the 2-position, and with further substitution at the 5, 6 and 7 positions, as elastase inhibitors. Uejima, et al. [J. Pharm. Exp. Ther., 265, 516-522 (1993)] describe 2-alkylamino-5-methyl-7-acylamino-4H-3.1-benzoxazin-4-ones as highly selective elastase inhibitors with significant plasma stability. U.S. Pat. No. 4,657,893, to A. Krantz et al, describes 2-alkylamino- and 2-alkylurido-4H-3,1-benzoxazin-4-ones having further substitution at the 5, 7 and 8 positions, as enzyme inhibitors.
F. L. M. Alvarez [An. Quim., 79, 115-17 (1993)] describes the preparation of 2-sulfonylamino-4H-3,1-benzoxazinones. J. G. Tercero et al. [An. Quim., 83, 247-50 (1987)] describe the preparation of 2-arylsulfonylamino-4H-3,1-benzoxazinones.
I. Butula et al. [Croat. Chem. Acta, 54, 105-8 (1981)] describe the synthesis of 2-alkylamino-4H-3,1-benzoxazinones. H. Ulrich et al. [J. Org Chem., 32, 4052-53 (1967)] describe the synthesis of 2-alkylamino-4H-3,1-benzoxazinones. E. Papadopoulos [J. Heterocyclic. Chem., 21, 1411-14 (1984)] describes the use of 2-haloalkylamino-4H-3,1-benzoxazin-4-one as a starting material for the synthesis of phenylureas. European Patent Application 466,944 (published Jan. 22, 1992).describes 2-alkylamino-7-acylamino-5-alkyl-4H-benzoxazin-4-ones as selective enzyme inhibitors of elastase.
M. Badawy et al. [,J. Heterocyclic. Chem., 21, 1403-4 (1984)] describe the use of N-phenyl-2-amino-4H-3,1-benzoxazin-4-one as a starting material for the synthesis of quinazolines. R. Khan and R. Rastogi [J. Chem. Research(S), 342-43 (1992)] describe the synthesis of 2-[5-aryl-1,3,4-oxadiazol-2-yl]amino-4H-3,1-benzoxazin-4-ones.
4H-3,1-Benzoxazin-4-ones have not previously been described as selective assemblin protease inhibitors or for the treatment and/or prophylaxis of viral infection.
The present invention relates to a class of substituted benzoxazinones, useful in the therapeutic and prophylactic treatment of viral infections, as defined by Formula I: 
wherein R and R2 are independently selected from hydrido, halo, alkyl, 
wherein R1 is a substituent selected from hydrido, halo, alkoxy, and alkyl;
wherein R3 is selected from hydrido, alkyl, alkylaminoalkyl, aralkyl, and heterocyclylalkyl;
wherein R4 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heterocyclyl, aralkyl, heterocyclylalkyl, 
or wherein xe2x80x94NR3R4 form a heterocyclic ring of 5 to 7 members;
wherein n is 0-6, inclusive;
wherein R5 and R6 are independently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, alkylaminoalkyl, aralkylaminoalkyl, alkoxyalkyl, and aralkoxyalkyl; or wherein xe2x80x94NR5R6 form a heterocyclic ring of 5 to 7 members;
wherein R7, R12 and R23 are independently selected from hydrido, alkyl, and aralkyl;
wherein R8, R9 and R14 are independently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, aminoalkyl, alkylaminoalkyl, carboxyalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, hydroxyalkyl, alkoxyalkyl, aralkoxyalkyl, alkylsulfonylalkyl, alkylsulfinylalkyl, alkylthioalkyl, aryl, aralkyl, aralkenyl, heterocyclyl, and heterocyclylalkyl; or wherein xe2x80x94NR8R9 form a heterocyclic ring of 5 to 7 members;
wherein R10 is selected from alkyl, haloalkyl, alkylaminoalkyl, carboxyalkyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, aralkoxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, alkylsulfonylalkyl, alkylsulfinylalkyl, alkylthioalkyl, aryl, aralkyl, heterocyclyl, and heterocyclylalkyl;
wherein R11 is alkyl;
wherein R13 is selected from amino, alkyl, alkylamino, alkylaminoalkyl and aryl;
wherein R15 is selected from hydrido, alkyl, hydroxyalkyl, alkoxyalkyl, aralkoxyalkyl, alkylaminoalkyl and N-aryl-N-alkylaminoalkyl;
wherein R16 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, guanidinylalkyl, carboxyalkyl, hydroxyalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aryl, heterocyclyl, aralkyl, heterocyclylalkyl, 
or wherein R15 and R16 together form cycloalkyl or heterocyclyl;
wherein R17 is selected from hydrido, alkyl, cycloalkyl and aralkyl;
wherein R18 and R19 are independently selected from hydrido, alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, heterocyclyl, aralkyl, heterocyclylalkyl, alkylaminoalkyl, and heterocyclylalkyl; or wherein xe2x80x94NR18R19 together form a heterocyclic ring of 5 to 7 atoms; or wherein R16 and R18 together form a saturated or partially unsaturated ring of 5 to 7 atoms;
wherein R20 is alkyl;
wherein R21, R22, R25, and R26 are independently selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, aminoalkyl, alkylaminoalkyl, hydroxyalkyl, alkoxyalkyl, aralkoxyalkyl, aryl, heterocyclyl, aralkyl, heterocyclylalkyl; or wherein xe2x80x94NR21R22 together form a heterocyclic ring of 5 to 7 atoms; or wherein xe2x80x94NR25R26 together form a heterocyclic ring of 5 to 7 atoms;
wherein R24 is selected from alkyl, cycloalkyl, cycloalkylalkyl, alkylaminoalkyl, aralkoxyalkyl, alkoxyalkyl, aryl, aralkyl, heterocyclyl, and heterocyclylalkyl; and
wherein R27 is selected from hydrido, alkyl, cycloalkyl, cycloalkylalkyl, alkylaminoalkyl, aminoalkyl, carboxyalkyl, aminocarbonylalkyl, hydroxyalkyl, aralkoxyalkyl, alkoxyalkyl, aryl, aralkyl, heterocyclyl, and heterocyclylalkyl;
or a pharmaceutically-acceptable salt or tautomer thereof.
The compounds of this invention have been shown to be particularly effective against herpetoviridae. Thus they are particularly useful for the treatment of herpes simplex viruses (HSV-1, HSV-2), cytomegalovirus (CMV), herpes varicella-zoster, Epstein-Barr, HHV6, HHV7, pseudorabies and rhinotracheitis, among others.
The invention further involves a method of treating a subject having a viral infection with an effective amount of a compound which can inhibit a virus-specific protease. Preferably, the subject is treated with a herpesvirus protease inhibitor. More preferred is a method wherein the viral protease inhibitor is a CMV protease inhibitor or an HSV protease inhibitor. Even more preferred is a method wherein the subject is treated with an inhibitor of CMV protease, encoded by UL80, HSV-1 protease or HSV-2 protease encoded by UL26, such as the 4H-3,1-benzoxazin-4-one compounds of the present invention.
Besides being useful for human treatment, these compounds are also useful for veterinary treatment of animals, including companion animals and farm animals, such as, but not limited to, horses, dogs, cats, cows, sheep and pigs.
The present compounds may also be used in co-therapies, partially or completely, in place of other conventional antiviral compounds, such as together with antivirals including but not limited to ganciclovir, docosanol, trifluridine, foscarnet, ribavirin, epervudine, interferon, thymostimulin, Ciba-Geigy CGP-16056, sprofen, Efalith, ibuprofen piconol, ufenamate, thymopentin, aciclovir, valaciclovir, edoxudine, famciclovir, idoxuridine, vidarabine, Epavir, zinc acetate, tromantadine, riodoxol, sorivudine, Yakult Honsha LC-9018, cidofovir, bromovinyldeoxyuridine, Lidakol, Stega Pharmaceutical cytokine-releasing agent, CSL ISCOM, penciclovir, Viraplex, Pharmacia and Upjohn THF, Boehringer Ingelheim BIRR-4, NIH peptide T, Virend, zinc glycerolate, and lobucavir.
The phrase xe2x80x9cfurther providedxe2x80x9d, as used in the claims, is intended to mean that the denoted proviso is not to be considered conjunctive with any of the other provisos. The phrase xe2x80x9ctherapeutically-effectivexe2x80x9d is intended to qualify the amount of the compound which will achieve the goal of improvement in severity and the frequency of incidence, while avoiding adverse side effects typically associated with alternative therapies. The phrase xe2x80x9ccombination therapyxe2x80x9d (or xe2x80x9cco-therapyxe2x80x9d), in defining use of a compound of the present invention and another agent, is intended to embrace administration of each agent in a sequential manner in a regimen that will provide beneficial effects of the drug combination, and is intended as well to embrace co-administration of these agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of these active agents or in multiple, separate capsules for each agent.
A preferred class of compounds consists of those compounds of Formula I wherein R and R2 are independently selected from hydrido, halo, lower alkyl, 
wherein R1 is a substituent selected from hydrido, halo, lower alkoxy, and lower alkyl; wherein R3 is selected from hydrido, lower alkyl, lower alkylaminoalkyl, lower aralkyl, and lower heterocyclylalkyl; wherein R4 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl, 
or wherein xe2x80x94NR3R4 form a heterocyclic ring of 5 to 7 members; wherein n is 0-6, inclusive; wherein R5 and R6 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, lower aralkyl, heterocyclyl, lower heterocyclylalkyl, lower alkylaminoalkyl, lower aralkylaminoalkyl, lower alkoxyalkyl, and lower aralkoxyalkyl; or wherein xe2x80x94NR5R6 form a heterocyclic ring of 5 to 7 members; wherein R7, R12 and R23 are independently selected from hydrido, lower alkyl, and lower aralkyl; wherein R8, R9 and R14 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower haloalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower alkylaminocarbonylalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower alkyl, lower aralkenyl, heterocyclyl, and lower heterocyclylalkyl; or wherein xe2x80x94NR8R9 form a heterocyclic ring of 5 to 7 members; wherein R10 is selected from lower alkyl, lower haloalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower aralkoxyalkyl, lower alkylaminocarbonylalkyl, lower alkoxyalkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; wherein R11 is lower alkyl; wherein R13 is selected from amino, lower alkyl, lower alkylamino, lower alkylaminoalkyl and aryl; wherein R15 is selected from hydrido, lower alkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylaminoalkyl and lower N-aryl-N-alkylaminoalkyl; wherein R16 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower haloalkyl, lower guanidinylalkyl, lower carboxyalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylthioalkyl, lower alkylsulfinylalkyl, lower alkylsulfonylalkyl, aryl, lower heterocyclyl, lower aralkyl, lower heterocyclylalkyl, 
or wherein R15 and R16 together form cycloalkyl or heterocyclyl; wherein R17 is selected from hydrido, lower alkyl, lower cycloalkyl and lower aralkyl; wherein R18 and R19 are independently selected from hydrido, lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl, lower alkylaminoalkyl, and lower heterocyclylalkyl; or wherein xe2x80x94NR18R19 together form a heterocyclic ring of 5 to 7 atoms; or wherein R16 and R18 together form a saturated or partially unsaturated ring of 5 to 7 atoms; wherein R20 is lower alkyl; wherein R21, R22, R25, and R26 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl; or wherein xe2x80x94NR21R22 together form a heterocyclic ring of 5 to 7 atoms; or wherein xe2x80x94NR25R26 together form a heterocyclic ring of 5 to 7 atoms; wherein R24 is selected from lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylaminoalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; and wherein R27 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylaminoalkyl, lower aminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower hydroxyalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; or a pharmaceutically-acceptable salt or tautomer thereof.
A more preferred class of compounds consists of those compounds of Formula I wherein R and R2 are independently selected from hydrido, halo, lower alkyl, 
wherein R1 is a substituent selected from hydrido, lower alkoxy and lower alkyl; wherein R3 is selected from hydrido, lower alkyl, lower alkylaminoalkyl, lower aralkyl, and lower heterocyclylalkyl; wherein R4 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl, 
or wherein xe2x80x94NR3R4 form a heterocyclic ring of 5 to 7 members; wherein n is 0-6, inclusive; wherein R5 and R6 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, lower aralkyl, heterocyclyl, lower heterocyclylalkyl, lower alkylaminoalkyl, lower aralkylaminoalkyl, lower alkoxyalkyl, and lower aralkoxyalkyl; or wherein xe2x80x94NR5R6 form a heterocyclic ring of 5 to 7 members; wherein R7, R12 and R23 are independently selected from hydrido, lower alkyl and lower aralkyl; wherein R8, R9 and R14 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower haloalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower alkylaminocarbonylalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower aralkyl, lower phenylalkenyl, heterocyclyl, and lower heterocyclylalkyl; or wherein xe2x80x94NR8R9 form a heterocyclic ring of 5 to 7 members; wherein R10 is selected from lower alkyl, lower haloalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, alkylaminocarbonylalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; wherein R11 is lower alkyl; wherein R13 is selected from amino, lower alkyl, lower alkylamino, lower alkylaminoalkyl and aryl; wherein R15 is selected from hydrido, and lower alkyl, wherein R16 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower haloalkyl, lower guanidinylalkyl, lower carboxyalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylthioalkyl, lower alkylsulfinylalkyl, lower alkylsulfonylalkyl, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl, 
or wherein R15 and R16 together form lower cycloalkyl or heterocyclyl; wherein R17 is selected from hydrido, lower alkyl, lower cycloalkyl and lower aralkyl; wherein R18 and R19 are independently selected from hydrido, lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl, lower alkylaminoalkyl, and lower heterocyclylalkyl; or wherein xe2x80x94NR18R19 together form a saturated, partially unsaturated or unsaturated ring of 5 to 7 atoms; or wherein R16 and R18 together form a saturated or partially unsaturated ring of 5 to 7 atoms; wherein R20 is lower alkyl; wherein R21, R22, R25, and R26 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower hydroxyalkyl, aryl, lower alkoxyalkyl, lower aralkoxyalkyl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl; or wherein xe2x80x94NR21R22 together form a heterocyclic ring of 5 to 7 atoms; or wherein xe2x80x94NR25R26 together form a heterocyclic ring of 5 to 7 atoms; wherein R24 is selected from lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylaminoalkyl, lower aralkoxyalkyl lower alkoxyalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; and wherein R27 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylaminoalkyl, lower aminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower hydroxyalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; or a pharmaceutically-acceptable salt or tautomer thereof.
An even more preferred class of compounds consists of those compounds of Formula I wherein R is a substituent selected from hydrido, halo, lower alkyl and 
wherein R1 is a substituent selected from hydrido, lower alkoxy and lower alkyl; wherein R2 is a substituent selected from hydrido, halo, lower alkyl, 
wherein R3 is selected from hydrido, lower alkyl, and lower aralkyl; wherein R4 is selected from 
or wherein xe2x80x94NR3R4 form a heterocyclic ring of 5 to 7 members; wherein n is 0-5, inclusive; wherein R5 and R6 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, lower aralkyl, heterocyclyl,.lower heterocyclylalkyl, lower alkylaminoalkyl, lower aralkylaminoalkyl, lower alkoxyalkyl, and lower aralkoxyalkyl;
or wherein xe2x80x94NR5R6 form a heterocyclic ring of 5 to 7 members; wherein R7, R12 and R23 are independently selected from hydrido, lower alkyl and lower aralkyl; wherein R8, R9 and R14 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower haloalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower alkylaminocarbonylalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower aralkyl, lower phenylalkenyl, heterocyclyl, and lower heterocyclylalkyl; or wherein xe2x80x94NR8R9 form a heterocyclic ring of 5 to 7 members; wherein R10 is selected from lower alkyl, lower haloalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, alkylaminocarbonylalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; wherein R11 is lower alkyl; wherein R13 is selected from amino, lower alkyl, lower alkylamino, lower alkylaminoalkyl and aryl; wherein R15 is selected from hydrido, and lower alkyl; wherein R16 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower haloalkyl, lower guanidinylalkyl, lower carboxyalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylthioalkyl, lower alkylsulfinylalkyl, lower alkylsulfonylalkyl, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl, 
or wherein R15 and R16 together form lower cycloalkyl or heterocyclyl; wherein R17 is selected from hydrido, lower alkyl, lower cycloalkyl and lower aralkyl; wherein R18 and R19 are independently selected from hydrido, lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkylalkyl1, aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl, lower alkylaminoalkyl, and lower heterocyclylalkyl; or wherein xe2x80x94NR18R19 together form a saturated, partially unsaturated or unsaturated ring of 5 to 7 atoms; or wherein R16 and R18 together form a saturated or partially unsaturated ring of 5 to 7 atoms; wherein R20 is lower alkyl; wherein R21, R22, R25, and R26 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower aryl, heterocyclyl, lower aralkyl, lower heterocyclylalkyl; or wherein xe2x80x94NR21R22 together form a heterocyclic ring of 5 to 7 atoms; or wherein xe2x80x94NR25R26 together form a heterocyclic ring of 5 to 7 atoms; wherein R24 is selected from lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylaminoalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; and wherein R27 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylaminoalkyl, lower aminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower hydroxyalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; or a pharmaceutically-acceptable salt or tautomer thereof.
A class of compounds of particular interest consists of those compounds of Formula I wherein R is a substituent selected from hydrido, bromo, iodo, methyl and 
wherein R1 is a substituent selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl; methoxy, ethoxy, propoxy, butoxy, and tert-butoxy; wherein R2 is a substituent selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, 
wherein R3 it selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, benzyl, phenylethyl and diphenylmethyl; wherein R4 is selected from 
or wherein xe2x80x94NR3R4 form a heterocyclic ring selected from pyrrolidinyl, piperidinyl, morpholino, piperazinyl and azepinyl; wherein n is 0-4, inclusive; wherein R5 and R6 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, phenyl, benzyl, furyl, thienyl, thiazolyl, pyrrolyl, furylmethyl, thienylethyl, thiazolylmethyl, pyrrolylmethyl, methylaminomethyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, benzylaminomethyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, and benzyloxymethyl; or wherein xe2x80x94NR5R6 form a heterocyclic ring selected from pyrrolidinyl, piperidinyl, morpholino, piperazinyl and azepinyl; wherein R7, R12 and R23 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, benzyl and phenylethyl; wherein R8, R9 and R14 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylpropyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl, methylamino, ethylamino, propylamino, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-diethylaminoethyl, N,N-diethylaminopropyl, carboxymethyl, carboxyethyl, carboxypropyl, aminocarbonylmethyl, N,N-dimethylaminocarbonylmethyl, hydroxymethyl, hydroxypropyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, benzyloxymethyl, methylsulfonylmethyl, methylsulfinylmethyl, methylthiomethyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl; isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, lower aralkyl selected from benzyl, naphthylmethyl, phenylethyl, and phenylisopropyl, wherein the phenyl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, lower phenylalkenyl selected from phenylethenyl, and phenylpropenyl, wherein the phenyl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, heterocyclyl selected from furyl, pyrrolyl, pyridyl, oxazolyl, pyrazolyl, isoxazolyl, thienyl, and thiazolyl, and lower heterocyclylalkyl_selected from thienylmethyl, morpholinylethyl, morpholinylmethyl, piperazinylethyl, piperdinylethyl, piperdinylmethyl, pyrrolidinylethyl, pyrrolidinylmethyl, pyrrolidinylpropyl, imidazolylethyl, oxazolylmethyl, thiazolylmethyl, furylmethyl, thienylethyl, and thiazolylmethyl, wherein the heterocyclyl moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; or wherein xe2x80x94NR8R9 form a heterocyclic ring selected from pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl and azepinyl; wherein R10 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl end dichloropropyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminoethyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, carboxymethyl, carboxyethyl, carboxypropyl, aminocarbonylmethyl, N,N-dimethylaminocarbonylmethyl, benzyloxymethyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylpropyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, methylsulfonylmethyl, methylsulfinylmethyl, methylthiomethyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, lower aralkyl selected from benzyl, phenethyl, naphthylmethyl, wherein the aryl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, methylenedioxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminoethyl, N,N-diethylaminobutyl, N,N-dimethylamino, N,N-dimethylamino, and N,N-diethylamino, heterocyclyl selected from furyl, thienyl, and thiazolyl, and lower heterocyclylalkyl selected from thienylmethyl, morpholinylethyl, morpholinylmethyl, piperazinylethyl, piperdinylethyl, piperdinylmethyl, pyrrolidinylethyl, pyrrolidinylmethyl, pyrrolidinylpropyl, imidazolylethyl, oxazolylmethyl, thiazolylmethyl, furylmethyl, thienylethyl, and thiazolylmethyl, wherein the heterocyclyl moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; wherein R1l is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, pentyl, and hexyl; wherein R13 is selected from phenyl, amino, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminoethyl, N,N-diethylaminobutyl, N,N-dimethylamino, N,N-dimethylamino, and N,N-diethylamino; wherein R15 is selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; wherein R16 is selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, mercaptoethyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, phenylmethoxymethyl, aminomethyl, aminohexyl, aminobutyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, mercaptomethyl, methylthioethyl, methylsulfonylethyl, phenyl optionally substituted at a substitutable position with one or more substituents independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, fluoro, chloro, bromo, iodo, nitro, amino, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, methylamino, and hexylamino, heterocyclyl selected from pyridyl, thienyl, morpholinyl, piperidinyl, indolyl, quinolinyl, pyrrolidinyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, and isoxazolyl, optionally substituted at a substitutable position with one or more substituents independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, tart-butoxy, fluoro, chloro, bromo, iodo, amino, oxo, N,N-dimethylamino, and N,N-diethylamino, lower aralkyl selected from benzyl, phenethyl and naphthylmethyl, wherein the aryl ring is optionally substituted at a substitutable position with one or more substituents independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, hydroxy, methoxy, ethoxy, propoxy, butoxy, tert-butoxy, fluoro, chloro, bromo, iodo, nitro, amino, methylamino, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, ethylamino, N,N-dimethylamino, N,N-dimethylamino, and N,N-diethylamino, lower heterocyclylalkyl selected from pyrrolidinylethyl, furylmethyl, pyrrolidinylmethyl, piperazinylmethyl, piperazinylethyl, imidazolylmethyl, indolylmethyl, morpholinylmethyl, morpholinylethyl quinolinylmethyl, thienylmethyl, thiazolylethyl and thiazolylmethyl, wherein the heterocyclyl moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl, 
or wherein R15 and R16 together form a ring selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; wherein R17 is selected from hydrido, methyl; ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, and benzyl; wherein R18 and R19 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, butenyl, propenyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, butenyl, phenyl, pyridyl, thienyl, morpholinyl, piperidinyl, indolyl, quinolinyl, pyrrolidinyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, benzyl, phenethyl, lower heterocyclylalkyl selected from furylmethyl, thienylmethyl, morpholinylethyl, piperazinylethyl, piperdinylethyl, pyrrolidinylethyl, pyrrolidinylpropyl, imidazolylethyl, oxazolylmethyl, and thiazolylmethyl, wherein the heterocyclyl moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methylaminomethyl, methylaminohexyl, ethylaminobutyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, and N,N-diethylaminobutyl; or wherein xe2x80x94NR18R19 together form a ring selected from piperazinyl, piperidinyl, pyrrolidinyl, azepinyl and morpholinyl, wherein the ring is optionally substituted at a substitutable position with one or more substituents independently selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; or wherein R16 and R18 together form a ring selected from 2-oxo-pyrrolidinyl and 2-oxo-piperidinyl; wherein R20 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, pentyl, and hexyl; wherein R21, R22, R25, and R26 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, propenyl, butenyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, pyridyl, thienyl, morpholinyl, piperidinyl, indolyl, quinolinyl, pyrrolidinyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, and isoxazolyl, benzyl, phenethyl, lower heterocyclylalkyl selected from furylmethyl, thienylmethyl, morpholinylethyl, piperazinylethyl, piperdinylethyl, pyrrolidinylethyl, pyrrolidinylpropyl, imidazolylethyl, oxazolylmethyl, and thiazolylmethyl, wherein the heterocyclyl moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methylaminomethyl, methylaminohexyl, ethylaminobutyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, and N,N-diethylaminobutyl; or wherein xe2x80x94NR21R22 together form a ring selected from piperazinyl, piperdinyl, pyrrolidinyl, azepinyl and morpholinyl; or wherein xe2x80x94NR25R26 together form a ring selected from piperazinyl, piperdinyl, pyrrolidinyl, azepinyl and morpholinyl; wherein R24 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, benzyloxyethyl, benzyloxymethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylethyl, cyclohexylpropyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, heterocyclyl selected from pyridyl, thienyl, morpholinyl, pyrimidyl, indolyl, isoquinolyl, quinolyl, tetrahydroquinolinyl, piperidinyl, pyrrolidinyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, and isoxazolyl, wherein the heterocyclyl is optionally substituted at a substitutable position with one or more substituents selected independently from lower alkyl, lower alkoxy, amino, halo, lower dialkylaminoalkyl, and lower dialkylamino, lower aralkyl selected from benzyl, phenethyl, and naphthylmethyl, wherein the aryl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, methylenedioxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, N,N-dimethylamino, and N,N-diethylamino, and lower heterocyclylalkyl selected from furylmethyl, pyrrolidinylmethyl, quinolinylmethyl, piperazinylmethyl, imidazolylmethyl, indolylmethyl, morpholinylmethyl, thienylmethyl, and thiazolylmethyl, wherein the heterocyclyl moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; and wherein R27 is selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, trifluoromethyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, phenylmethoxymethyl, benzyloxyethyl, aminomethyl, aminohexyl, aminobutyl, carboxyethyl, carboxypropyl, carboxymethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylethyl, cyclohexylpropyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, heterocyclyl selected from pyridyl, thienyl, morpholinyl, pyrimidyl, indolyl, isoquinolyl, quinolyl, tetrahydroquinolinyl, piperidinyl, pyrrolidinyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, and isoxazolyl, wherein the heterocyclyl is optionally substituted at a substitutable position with one or more substituents selected independently from lower alkyl, lower alkoxy, amino, halo, lower dialkylaminoalkyl, and lower dialkylamino, lower aralkyl selected from benzyl, phenethyl, and naphthylmethyl, wherein the aryl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, N,N-dimethylamino, and N,N-diethylamino, and lower heterocyclylalkyl1y selected from furylmethyl, pyrrolidinylmethyl, quinolinylmethyl, piperazinylmethyl, imidazolylmethyl, indolylmethyl, morpholinylmethyl, thienylmethyl, and thiazolylmethyl, wherein the heterocyclyl moiety- may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; or a pharmaceutically-acceptable salt or tautomer thereof.
Another more preferred class of compounds consists of those compounds of Formula I wherein R is a substituent selected from hydrido, halo, lower alkyl and 
wherein R1 is a substituent selected from hydrido, lower alkoxy and lower alkyl; wherein R2 is a substituent selected from hydrido, halo, lower alkyl, 
wherein R3 is selected from hydrido, lower alkyl, and lower aralkyl; wherein R4 is selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, heterocyclyl, lower aralkyl and lower heterocyclylalkyl; or wherein xe2x80x94NR3R4 form a heterocyclic ring of 5 to 7 members; wherein n is 0-5, inclusive; wherein R5 and R6 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, aryl, lower aralkyl, heterocyclyl, lower heterocyclylalkyl, lower alkylaminoalkyl, lower aralkylaminoalkyl, lower alkoxyalkyl, and lower aralkoxyalkyl; or wherein xe2x80x94NR5R6 form a heterocyclic ring of 5 to 7 members; wherein R7 and R12 are independently selected from hydrido, lower alkyl and lower aralkyl; wherein R8, R9 and R14 are independently selected from hydrido, lower alkyl, lower cycloalkyl, lower cycloalkylalkyl, lower haloalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, lower alkylaminocarbonylalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower aralkoxyalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower aralkyl, lower phenylalkenyl, heterocyclyl, and lower heterocyclylalkyl; or wherein xe2x80x94NR8R9 form a heterocyclic ring of 5 to 7 members; wherein R10 is selected from lower alkyl, lower haloalkyl, lower alkylaminoalkyl, lower carboxyalkyl, lower aminocarbonylalkyl, alkylaminocarbonylalkyl, lower aralkoxyalkyl, lower alkoxyalkyl, lower cycloalkyl, lower cycloalkylalkyl, lower alkylsulfonylalkyl, lower alkylsulfinylalkyl, lower alkylthioalkyl, aryl, lower aralkyl, heterocyclyl, and lower heterocyclylalkyl; wherein R11 is lower alkyl; and wherein R13 is selected from amino, lower alkyl, lower alkylamino, lower alkylaminoalkyl and aryl; or a pharmaceutically-acceptable salt or tautomer thereof.
A class of compounds of particular interest consists of those compounds of Formula I wherein R is a substituent selected from hydrido, bromo, iodo, methyl and 
wherein R1 is a substituent selected from hydrido, meth ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxy, ethoxy, propoxy, butoxy, and tert-butoxy; wherein R2 is a substituent selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, 
wherein R3 is selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, benzyl, phenylethyl and diphenylmethyl; wherein R4 is selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylethyl, cyclohexylpropyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from fluoro, chloro, iodo, bromo, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, lower alkoxy, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethoxy, N,N-dimethylaminohexyloxy, and N,N-diethylaminobutoxy, lower aralkyl selected from benzyl, naphthylmethyl, phenylethyl, and phenylisopropyl, wherein the phenyl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, heterocyclyl selected from methylpiperidinyl, methylazabicyclooctanyl, morpholinyl, pyrrolidinyl, and piperazinyl, phenylmethyl, phenylethyl, and lower heterocyclylalkyl selected from pyridylmethyl, pyridylmethyl, furylmethyl, thienylmethyl, and thiazolylmethyl, where the heterocyclic rings are optionally substituted at a substitutable position with one or more substituents selected independently from fluoro, chloro, iodo, bromo, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, lower alkoxy, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethoxy, N,N-dimethylaminohexyloxy, and N,N-diethylaminobutoxy; or wherein xe2x80x94NR3R4 form a heterocyclic ring selected from pyrrolidinyl, piperidinyl, morpholino, piperazinyl and azepinyl; wherein n is 0-4, inclusive; wherein R5 and R6 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, phenyl, benzyl, furyl, thienyl, thiazolyl, pyrrolyl, furylmethyl, thienylethyl, thiazolylmethyl, pyrrolylmethyl, methylaminomethyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, benzylaminomethyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, and benzyloxymethyl; or wherein xe2x80x94NR5R6 form a heterocyclic ring selected from pyrrolidinyl, piperidinyl, morpholino, piperazinyl and azepinyl; wherein R7 and R12 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, benzyl and phenylethyl; wherein R8, R9 and R14 are independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylpropyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl, methylamino, ethylamino, propylamino, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-diethylaminoethyl, N,N-diethylaminopropyl, carboxymethyl, carboxyethyl, carboxypropyl, aminocarbonylmethyl, N,N-dimethylaminocarbonylmethyl, hydroxymethyl, hydroxypropyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, benzyloxymethyl, methylsulfonylmethyl, methylsulfinylmethyl, methylthiomethyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, lower aralkyl selected from benzyl, naphthylmethyl, phenylethyl, and phenylisopropyl, wherein the phenyl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, lower phenylalkenyl selected from phenylethenyl, and phenylpropenyl, wherein the phenyl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, heterocyclyl selected from furyl, pyrrolyl, pyridyl, oxazolyl, pyrazolyl, isoxazolyl, thienyl, and thiazolyl, and lower heterocyclylalkyl selected from thienylmethyl, morpholinylethyl, morpholinylmethyl, piperazinylethyl, piperdinylethyl, piperdinylmethyl, pyrrolidinylethyl, pyrrolidinylmethyl, pyrrolidinylpropyl, imidazolylethyl, oxazolylmethyl, thiazolylmethyl, furylmethyl, thienylethyl, and thiazolylmethyl, wherein the heterocyclyl moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; or wherein xe2x80x94NR8R9 form a heterocyclic ring selected from pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl and azepinyl; wherein R10 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminopropyl, N,N-dimethylaminohexyl, N,N-diethylaminoethyl, N,N-diethylaminopropyl, N,N-diethylaminobutyl, carboxymethyl, carboxyethyl, carboxypropyl, aminocarbonylmethyl, N,N-dimethylaminocarbonylmethyl, benzyloxymethyl, methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl, methoxypropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylpropyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, methylsulfonylmethyl, methylsulfinylmethyl, methylthiomethyl, phenyl optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminohexyl, N,N-diethylaminobutyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, N,N-dimethylamino, and N,N-diethylamino, lower aralkyl selected from benzyl, phenethyl, naphthylmethyl, wherein the aryl ring is optionally substituted at a substitutable position with one or more substituents selected independently from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, methylenedioxy, tert-butoxy, amino, fluoro, chloro, bromo, iodo, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminoethyl, N,N-diethylaminobutyl, N,N-dimethylamino, N,N-dimethylamino, and N,N-diethylamino, heterocyclyl selected from furyl, thienyl, and thiazolyl, and lower heterocyclylalkyl selected from thienylmethyl, morpholinylethyl, morpholinylmethyl, piperazinylethyl, piperdinylethyl, piperdinylmethyl, pyrrolidinylethyl, pyrrolidinylmethyl, pyrrolidinylpropyl, imidazolylethyl, oxazolylmethyl, thiazolylmethyl, furylmethyl, thienylethyl, and thiazolylmethyl, wherein the heterocyclyl Moiety may be substituted at a substitutable position with a radical selected from fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl; wherein R11 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, pentyl, and hexyl; and wherein R13 is selected from phenyl, amino, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl N,N-dimethylaminomethyl, N,N-dimethylaminoethyl, N,N-dimethylaminohexyl, N,N-diethylaminoethyl, N,N-diethylaminobutyl, N,N-dimethylamino, N,N-dimethylamino, and N,N-diethylamino; or a pharmaceutically-acceptable salt or tautomer thereof.
Within Formula I there is a subclass of compounds of high interest represented by Formula II: 
wherein R28 is selected from (a) amino optionally substituted with one or two radicals selected from alkyl, aralkyl, heterocyclylalkyl, heterocyclyl, and aryl, and (b) amino acid residues and derivatives thereof;
wherein R29 is selected from hydrido, alkyl, halo, 
wherein R30 is selected from alkyl, alkoxy, alkylamino, carboxyalkyl, alkoxyalkyl, alkylaminoalkyl, cycloalkyl, heterocyclyl, heterocyclylalkyl, aralkyl, aralkoxy, aryloxy, cycloalkyloxy, arylamino, aralkenyl, heterocyclylalkoxy, alkylaminoalkoxy, alkylaminoalkylamino, heterocyclylalkylamino, N-aryl-N-alkylamino, and N-aralkylamino; wherein R31 is alkyl; wherein R32 is selected from alkyl and aryl; and wherein R33 is selected from hydrido, halo and alkyl; or a pharmaceutically-acceptable salt thereof.
An even more preferred class of compounds consists of those compounds of Formula II wherein R28 is selected from (a) amino optionally substituted with one or two radicals selected from lower alkyl, lower aralkyl, lower heterocyclylalkyl, heterocyclyl, and aryl, wherein R24 is selected from hydrido, lower alkyl, halo, 
wherein R30 is selected from lower alkyl, lower alkoxy, lower alkylamino, lower carboxyalkyl, lower alkoxyalkyl, lower alkylaminoalkyl, lower cycloalkyl, heterocyclyl, lower heterocyclylalkyl, lower heterocyclylalkoxy, lower aralkenyl, lower aralkyl, lower aralkoxy, phenyloxy, phenylamino, lower cycloalkyloxy, lower N-phenyl-N-alkylamino, lower alkylaminoalkoxy, lower alkylaminoalkylamino, lower heterocyclylalkylamino, and lower N-aralkylamino; wherein R31 is lower alkyl; wherein R32 is selected from lower alkyl and aryl; and wherein R33 is selected from hydrido and lower alkyl; or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formulas I and II consists of compounds and pharmaceutically-acceptable salts thereof as follows:
xcex1S-[(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl) amino]-4-methoxy-N-methyl-N-(phenylmethyl)benzenepropanamide;
1,1-dimethylethyl[2-[[2-(dimethylamino)-1S-[(4-iodophenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-(diethylamino)-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-[[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]methyl]ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(4-methoxyphenyl)methyl]-2-oxo-2-[[(2-pyridinyl)methyl]amino]ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(4-methoxyphenyl)methyl]-2-oxo-2-[[2-(2-pyridinyl)ethyl]amino]ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-[ethyl(phenylmethyl)amino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-[ethyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-(4-morpholinyl)-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-8-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[2-[ethyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-2-[[2-(methylphenylamino)-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-(ethylphenylamino)-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[2-[ethyl(phenylmethyl)amino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[(4-chlorophenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(2-phenylethyl)amino]-2-oxoethyl]amino -5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[2-[(4-chlorophenyl)methylamino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-2-[[2-[methyl[(3-pyridinyl)methyl]amino]-1S-(phenylmethyl)-2-oxoethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-(4-methylphenylamino)-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[2-(4-ethylphenylamino)-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-2-[[2-[methyl(2-phenylethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
xcex1S-[(6-amino-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)amino]-N-ethyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[(6-amino-8-bromo-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)amino]-N-ethyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[(6-amino-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)amino]-N-methyl-4-methoxy-N-(phenylmethyl)benzenepropanamide;
N-[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]pyrrolidine-1-acetamide;
N-[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]pyridine-3-propanamide;
4-methoxy-N-methyl-xcex1S-[[5-methyl-4-oxo-6-[[[[[(4-pyridinyl)methyl]amino]carbonyl]amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
N-[[2-([1S-[(4-methoxyphenyl)methyl]-2-[methyl (phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]pyridine-4-propanamide;
ethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
2-methylpropyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
phenylmethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
phenyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
ethyl[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
xcex1S-[[6-[[(2,2-dimethyl-1-oxopropyl)amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-4-methoxy-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[6-[[(3,3-dimethyl-1-oxobutyl)amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-4-methoxy-N-methyl-N-(phenylmethyl)benzenepropanamide;
N-[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]morpholine-4-acetamide;
xcex1S-[[6-[[[[4-(dimethylamino)phenyl]acetyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-4-methoxy-N-methyl-N-(phenylmethyl)benzenepropanamide;
phenylmethyl[[2-[[2-[ethyl(phenylmethyl)amino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
phenyl[[2-[[2-[ethyl(phenylmethyl)amino-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
phenylmethyl[[5-methyl-2-[[2-[methyl (phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
N-[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]pyridine-2-carboxamide;
phenylmethyl[[2-([1S-[(4-chlorophenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethylamino-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
4-methoxy-N-methyl-xcex1S-[[5-methyl-6-[[(1-oxo-3-phenylpropyl)amino]methyl]-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-6-[[(1-oxo-3-phenyl-2-propenyl)amino]methyl]-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-6-[[(1-oxo-3-phenylpropyl)amino]-methyl]-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[6-[(acetylamino)methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
phenylmethyl[[2-[[2-[[(2-chlorophenyl)methyl]ethylamino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
phenylmethyl[[5-methyl-2-[[2-methyl[(3-pyridinyl)methyl]amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
N-methyl-xcex1S-[[5-methyl-4-oxo-6-[[(1-oxo-3-phenylpropyl)amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(3-pyridinylmethyl)benzenepropanamide;
phenylmethyl[[2-[[2-[ethyl[(2-fluorophenyl)methyl]amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
phenylmethyl[[2-[[2-[[(2-chlorophenyl)methyl]methylamino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
phenylmethyl[[5-methyl-2-[[2-[methyl(2-phenylethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
N-[2- [[1S-[A-methoxyphenyl)methyl]-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]thiophene-2-acetamide;
N-[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]pyridine-2-carboxamide;
phenyl[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4H-3,1-benzoxazin-6-yl]carbamate;
ethyl[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4H-3,1-benzoxazin-6-yl]carbamate;
2-methylpropyl[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4H-3,1-benzoxazin-6-yl]carbamate;
phenylmethyl[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4H-3,1-benzoxazin-6-yl]carbamate;
N-[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]furan-2-carboxamide;
phenyl[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
xcex1S-[[6-[[[[(1,1-dimethylethyl)amino]carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-4-methoxy-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[6-[[[[(1,1-dimethylethyl)amino]carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-4-oxo-6-E[[(phenylamino)carbonyl]amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-4-oxo-6-[[[[(1R-phenylethyl)amino]carbonyl]amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-4-oxo-6-[[[[(phenylmethyl)amino]carbonyl]aminomethyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-6-[[[(methylphenylamino)carbonyl]amino]methyl]-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
4-methoxy-N-methyl-xcex1S-[[5-methyl-4-oxo-6-[[[[(phenylmethyl)amino]carbonyl]amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
4-methoxy-N-methyl-xcex1S-[[5-methyl-4-oxo-6-[[(phenylsulfonyl)amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
4-methoxy-N-methyl-xcex1S-[[5-methyl-4-oxo-6-[(phenylsulfonyl)amino]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[8-bromo-5-methyl-6-[[[(4-methylphenyl)sulfonyl]amino]methyl]-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-4-oxo-6-[[(phenylsulfonyl)amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
1,1-dimethylethyl[[8-bromo-5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
xcex1S-[[8-bromo-6-[[[2-(dimethylamino)acetyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N(phenylmethyl)benzenepropanamide;
ethyl[[8-bromo-5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[8-bromo- 5 -methyl-2 -[[2 -[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
phenylmethyl[[8-bromo-5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
N-[[8-bromo-5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]morpholine-4-acetamide;
1,1-dimethylethyl[[8-bromo-2-[[2-ethyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
N-[[8-bromo-2-[[2-[ethyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]morpholine-4-acetamide;
xcex1S-[[8-bromo-6-[[[[(1,1-dimethylethyl)amino]carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[8-bromo-5-methyl-4-oxo-6-[[[[(1R-phenylethyl)amino]carbonyl]amino]methyl]-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[8-bromo-5-methyl-6-[[(methylsulfonyl)amino]methyl]-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
phenylmethyl[[8-bromo-5-methyl-2-[[2-[methyl(2-phenylethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[8-bromo-2-[[2-[ethyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate,
1,1-dimethylethyl[[8-bromo-2-[[2-[ethyl(phenylmethyl)amino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
phenyl[[8-bromo-2-[[2-[ethyl(phenylmethyl)amino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
phenylmethyl[[8-bromo-2-[[2-[ethyl(phenylmethyl)amino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
xcex1S-[[6-(dimethylamino)-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[6-(dimethylamino)-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-4-methoxy-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[6-(dimethylamino)-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-ethyl-4-methoxy-N-phenylbenzenepropanamide;
N-(4-chlorophenyl)-xcex1S-[[6-(dimethylamino)-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-4-methoxy-N-methylbenzenepropanamide;
xcex1S-[[8-bromo-5-methyl-4-oxo-6-[(phenylmethyl)amino]-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[8-bromo-6-(dimethylamino)-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[8-bromo-5-methyl-4-oxo-6-[(phenylmethyl)amino]-4H-3,1-benzoxazin-2-yl]amino]-N-ethyl-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[6-[bis(phenylmethyl)amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methyl-N-(phenylmethyl)benzenepropanamide;
N-methyl-xcex1S-[[5-methyl-4-oxo-6-[(phenylmethyl)amino]-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
4-methoxy-N-methyl-xcex1S-[[5-methyl-4-oxo-6-[(phenylmethyl)amino]-4H-3,1-benzoxazin-2-yl]amino]-N-(phenylmethyl)benzenepropanamide;
xcex1S-[[6-[bis(phenylmethyl)amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-4-methoxy-N-methyl-N-(phenylmethyl)benzenepropanamide;
3-pyridinylmethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
2-(1-piperidinyl)ethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
2-(4-morpholinyl)ethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
2-(dimethylamino)ethyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4 -oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
(4-pyridinyl)methyl[[2-[[1S-[(4-methoxyphenyl)methyl]-2-[methyl(phenylmethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-3,1-benzoxazin-6-yl]methyl]carbamate;
3-pyridinylmethyl[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
cyclopentyl[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
2-(dimethylamino)ethyl[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
2-(4-morpholinyl)ethyl[[5-methyl-2-[[2-[methyl(phenylmethyl)amino]-2-oxo-1S-(phenylmethyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
phenylmethyl[[2-[[2-[ethyl(phenylmethyl)amino]-1S-[(4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5,8-dimethyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
5-methoxy-2-[[(1R)-1-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
1,1-dimethylethyl[5-methyl-2-[(1-methylpiperidin-4-yl)amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[8-methyl-8-azabicyclo[3.2.1]octan-3-yl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-4-oxo-2[[1S-(4-bromophenyl)ethyl]amino]-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-4-oxo-2[[1S-(3-pyridinyl)ethyl]amino]-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[2-[2-(dimethylamino)ethoxy]pyridin-5-yl]ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-4-[2-(dimethylamino)ethyl]phenyl]ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl N-methyl-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]4H-3,1-benzoxazin-6-yl]carbamate;
N1-ethyl-N2-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]urea;
N1-[2-(dimethylamino)ethyl]-N2-(5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]urea;
N1-[2-(dimethylamino)ethyl]-N2-[[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]methyl]urea;
2-(dimethylamino)-N-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]acetamide;
N-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]pyrrolidine-1-acetamide;
N-methyl-N-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]pyrrolidine-1-acetamide;
N-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]morpholine-4-acetamide;
4-methyl-N-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]piperazine-1-acetamide;
1-methyl-N-[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]pyrrolidine-2S-carboxamide;
1,1-dimethylethyl[[5-methyl-4-oxo-2[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-4-oxo-2[[1S-(3-pyridinyl)ethyl]amino]-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1, 1-dimethylethyl[[2-[[1S-[4-[2-(dimethylamino)ethyl]phenyl]ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
2-(dimethylamino)-N-[[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]methyl]acetamide;
N-[[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]methyl]pyrrolidine-1-acetamide;
N-[[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]methyl]morpholine-4-acetamide;
4-methyl-N-[[5-methyl-4-oxo-2-[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]methyl]piperazine-1-acetamide;
1-methyl-N-[[5-methyl-4-oxo-2[(1S-phenylethyl)amino]-4H-3,1-benzoxazin-6-yl]methyl]pyrrolidine-2S-carboxamide;
6-bromo-5-methyl-2-[[(1R)-1-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
2-ethylamino-5-methyl-4H-3,1-benzoxazin-4-one;
2-[(1-methylethyl)amino]-5-methyl-4H-3,1-benzoxazin-4-one;
5-methyl-2-[[(1S) -1-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
5-methyl-2-[[(1R) -1-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
5-methyl-2-(phenylamino)-4H-3,1-benzoxazin-4-one;
2-[(3-chlorophenyl)amino]-5-methyl-4H-3,1-benzoxazin-4-one;
2-[(2,6-dichlorophenyl)amino]-5-methyl-4H-3,1-benzoxazin-4-one;
5-methyl-2-[(2-nitrophenyl)amino]-4H-3,1-benzoxazin-4-one;
5-methyl-2-[(4-nitrophenyl)amino]-4H-3 ,1-benzoxazin-4-one;
6-iodo-2[[(1R)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
2-[(2,6-dichlorophenyl)amino]-6-iodo-4H-3,1-benzoxazin-4-one;
2-[[(1S)-phenylethyl]amino]-6-iodo-4H-3,1-benzoxazin-4-one;
6-chloro-2-[[(1R)-phenylethyl]amino]-4H-3 ,1-benzoxazin-4-one;
6-methyl-2-[[(1R)phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
6-methyl-2-[[(1R) -phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
2-[[(1R)-(4-bromophenyl)ethyl]amino]-5-methyl-4H-3,1-benzoxazin-4-one;
2-(diethylamino)-5-methyl-4H-3,1-benzoxazin-4-one;
5-methyl-2-[N-methyl-N-(phenylmethyl)amino]-4H-3,1-benzoxazin-4-one;
5-methyl-2-[N-methyl-N-(2-pyridylmethyl)amino]-4H-3,1-benzoxazin-4-one;
6-bromo-5-methyl-2-[N-methyl-N-(phenylmethyl)amino-4H-3,1-benzoxazin-4-one;
6-[[(1,1-dimethylethoxy)carbonyl]amino]-1S-methyl-2-[[(1S)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-2-[[(1R)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-2-[[(1S)-phenylethylamino]-4H-3,1-benzoxazin-4-one;
6-amino-5-methyl-2-[[(1R)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
6-amino-5-methyl-2-[[(1S)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one,;
6-amino-methyl-5-methyl-2-[[(1S)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
6-[[[dimethylaminomethyl]carbonyl]amino]methyl]-5-methyl-2-[[(1S)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
5-methyl-2-[[(1R)-(4-iodophenyl)ethyl]amino]-4H-3,1-benzoxazin-4-one;
5-methyl-6-[[(1-morpholinylmethyl)carbonyl]amino]-2-[[(1S)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
6-[[(2-furanyl)carbonyl]amino]-5-methyl-2-[[(1S)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
5-methyl-2[[(1S)-phenylethyl]amino]-6-[[(1-pyrrolidinylmethyl)carbonyl]amino]-4H-3,1-benzoxazin-4-one;
5-methyl-6-[[(dimethylaminomethyl)carbonyl]amino]-2-[[(1S)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
5-methyl-6-[[(3-dimethylaminopropyl)carbonyl]amino]-2-[[(1R)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
6-[[[[(1R)-phenylethyl]amino]carbonyl]amino]-5-methyl-2-[[(1R)-phenylethyl]amino]-4H-3,1-benzoxazin-4-one;
1,1-dimethylethyl[2-[[2-(3,5-diiodo-4-methoxy phenyl)-1S-[(dimethylamino)methyl]ethylamino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(dimethylamino)methyl]-3-(methylsulfonyl)propyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-(dimethylamino)-1S-methylethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[[2-[[2-(dimethylamino)-1S-methylethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
N-[5-methoxy-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, N-methyl-N-phenylmethylamide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-3,5-diiodo-L-tyrosine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl-]-3,5-diiodo-O-methyl-L-tyrosine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl-]-3,5-diiodo-N, O-dimethyl-L-tyrosine, methyl ester;
3,5-dibromo-N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl-]-O-methyl-L-tyrosine, methyl ester;
methyl xcex1S-[[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-propanoate;
methyl xcex1S-[[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]oxazole-4-propanoate;
methyl 4-[(aminocarbonyl)amino]-2S-[[6[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]butanoate;
N2-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-asparagine, methyl ester;
N2-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5 -methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-glutamine, methyl ester;
1,1-dimethylethyl [2-[[2-(diethylamino)-1S-[(4-hydroxy-3,5-diiodophenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(4-hydroxy-3,5-diiodophenyl)methyl]2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-(diethylamino)-1S-methyl-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1,1-dimethyl-2-oxo-2-(pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-2-[[3-(methylsulfonyl)-1S-[(1-pyrrolidinyl)carbonyl]propyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-(diethylamino)-1S-[ (3,5-diiodo-4-methoxyphenyl)methyl]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl [5-methyl-2-[[1S-methyl-2-oxo-2-(1-pyrrolidinyl ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(3,5-diiodo-4-methoxyphenyl)methyl]-2-[(i-methylethyl)amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(4-hydroxy-3,5-diiodophenyl)methyl]-2 -(4-morpholinyl)-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2[[1s-[(4-hydroxy-3,5-diiodophenyl)methyl]-2-(4-methylpiperazin-1-yl)-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(4-hydroxy-3,5-diiodophenyl)methyl]-2-[[2-(dimethylamino)ethyl]methyl amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-[[2-(dimethylamino)ethyl]methylamino]-1S-methyl-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[2-[[2-(dimethylamino)ethyl]methylamino]-1,1-dimethyl-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[[[2-(dimethylamino)ethyl]methylamino]carbonyl]-3-(methylsulfonyl)propyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[(3,5-diiodo-4-methoxy phenyl)methyl]-2-[methyl[2-(1-piperidinyl)ethyl]amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-methyl-[2-(1-piperidinyl)ethyl]amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[[methyl-[2-(1-piperidinyl)ethyl]amino]carbonyl]-3-(methylsulfonyl)propyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[3,5-diiodo-4-methoxyphenyl)methyl]-2-[[methyl[2-(4-morpholinyl)ethyl]amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[2-[[1S-[[methyl-[2-(4-morpholinyl)ethyl]amino]carbonyl]-3-(methylsulfonyl)propyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-2-[[1S-methyl-2-[methyl-[2-(4-methylpiperazin-1-yl)ethyl]amino]-2-oxoethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-2-[[1S-methyl-2-[methyl-[2-(4-methylpiperazin-1-yl)ethyl]amino]carbonyl]-3-(methylsulfonyl)propyl]amino]-4-oxo-4R-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-4-oxo-2-[[3-oxo-1S-(3-pyridinyl)-3-(1-pyrrolidinyl)propyl]amino]-4H-3,1-benzoxazin-6-yl]carbamate;
1,1-dimethylethyl[5-methyl-2-[1S-methyl-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
methyl xcex1S-[[6-[1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]morpholine-4-butanoate;
methyl xcex1S-[[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]pyrrolidine-1-butanoate;
1,1-dimethylethyl[6-[[1S-[(4-hydroxy-3,5-diiodophenyl)methyl]-1-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]carbamate;
N-[2-(dimethylamino)ethyl]-as-[[6-[[(ethylamino)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-3,5-diiodo-4-methoxy-N-methylbenzenepropanamide;
N-[2-dimethylamino)ethyl]-xcex1S-[[6-[[ethyl amino)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]-N-methylpropanamide;
N-[2-(dimethylamino)ethyl]-3,5-diiodo-4-methoxy-N-methyl-xcex1S [[5-methyl-4-oxo-6-[(propylsulfonyl)amino]-4H-3,1-benzoxazin-2 -yl]amino]-N-methylpropanamide;
N1[2-(dimethylamino)ethyl]-N2-[2-[[1S-[(4-hydroxy-3,5-diiodophenyl)methyl]-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-1,1-benzoxazin-6-yl]urea;
2-(dimethylamino)ethyl[2-[[1S-[(3,5-diiodo-4-methoxyphenyl)ethyl]-2-oxo-2(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-9-yl]carbamate;
N1-[2-(dimethylamino)ethyl]-N2-[5-methyl-4-oxo-2-[[1S-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]]-4H-3,1-benzoxazin-6-yl]urea;
N1-[2-(dimethylamino)ethyl]-N2-[5-methyl-2-[[3-(methylsulfonyl)-1S-[(1-pyrrolidinyl)carbonyl]propyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]urea;
(3-pyridinyl)methyl[2-[[1S-[3,5-diiodo-4-methoxyphenyl)methyl]-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-a3,1-benzoxazin-6-yl]carbamate;
2-(dimethylamino)-N-[2-[[1S-[(3,5-diiodo-4-methoxyphenyl)methyl]-2-oxo-2-(4-morpholinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]acetamide;
2-(dimethylamino)-N-[5-methyl-2[[1S-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]acetamide;
N-[2-[[1S-[(3,5-diiodo-4-methoxyphenyl)methyl]-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl morpholine-4-acetamide;
N-[2-[[1,1-dimethyl-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]morpholine-4-acetamide;
N-[5-ethyl-2-[[3-(methylsulfonyl)-1S-[(1-pyrrolidinyl)carbonyl]propylamino -4-oxo-4H-3,1-benzoxazin-6-yl]morpholine-4-acetamide;
4-methyl-N-[5-methyl-2-[[1S-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]piperazine-1-acetamide;
N-[2-[[1S-[(3,5-diiodo-4-methoxyphenyl)methyl]-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]-1-methylpyrrolidine-2S-carboxamide;
N-[5-methyl-2-([1S-methyl-2-oxo-(4-morpholinyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]pyrrolidine-1-acetamide;
N-[5-methyl-2-[3-(methylsulfonyl)-1S-[(1-pyrrolidinyl)carbonyl]propyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl pyrrolidine-1-acetamide;
N-[5-methyl-2-[[3-(methylsulfonyl)-1S-[(4-methyl piperazin-1-yl)carbonyl]propyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]furan-2-carboxamide;
N-[6[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-3,5-diiodo-O-methyl-L-tyrosine, methyl ester;
methyl xcex1S-[6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]amino]thiazole-4-propanoate;
N2-[6[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-asparagine, methyl ester;
1-dimethylethyl[[5-methyl-2-[[3-methylsulfonyl)-1S-[(1-pyrrolidinyl)carbonyl]propyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[3,5-diiodo-4-methoxy phenyl)methyl]-2-[[2-(dimethylamino)ethyl]methyl amino]-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-([2-[[2-(dimethylamino)ethyl]methylamino]-1S-methyl-2-oxoethyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[2-[[1S-[[2-(dimethylamino)ethyl]methylamino]carbonyl]-3-(methylsulfonyl)propyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-2-[[1S-methyl-2-[methyl[2-(1-piperidinyl)ethyl]amino]-2-oxoethyl]-amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-2-[[1S-[[methyl-[2-(4-morpholinyl)ethyl]amino]carbonyl]-3-(methyl sulfonyl)propyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
1,1-dimethylethyl[[5-methyl-2-[[1S-methyl-[2-(4-methyl-1-piperazinyl)ethyl]amino]-2-oxoethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]carbamate;
Nl-[2-(dimethylamino)ethyl]-N2-[[5-methyl-2-[[1S-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]urea;
2-(dimethylamino)-N-[[5-methyl-2-[[1S-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]acetamide;
N-[[5-methyl-2-[[3-(methylsulfonyl)-1S-(1-pyrrolidinyl)carbonyl]propyl]amino]-4-oxo-4H-3,1-benzoxazin-6-yl]methyl]morpholine-4-acetamide;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-alanine, tert-butyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-D-alanine, 1,1-dimethyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-alanine, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-D-alanine, methyl ester;
N-5 (5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-valine, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-leucine, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-norleucine, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-isoleucine, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-methionine, methyl ester;
Nxcex1-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-Nxcex5-[(phenylmethoxy)carbonyl]-L-lysine, 1,1-dimethylethyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-phenylalanine, 1,1-dimethylethyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-phenylalanine, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-tyrosine, 1,1-dimethylethyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-tryptophan, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-tryptophan, 1,1-dimethylethyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-phenylglycine, 1,1-dimethylethyl ester;
2-[[2-methoxy-(1S)-(1-phenylmethyl)ethyl]amino]-5-methyl-4H-3,1-benzoxazin-4-one;
3,5-diiodo-N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-tyrosine, methyl ester;
N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-O-methyl-L-tyrosine, methyl ester;
N-(6-bromo-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-alanine, 1,1-dimethylethyl ester;
N(6-bromo5methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-D-alanine, 1,1-dimethylethyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, 1,1-dimethylethyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-(phenylmethyl)-L-serine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, dimethylamide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-thiazol-4-yl-alanine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-aspartic acid, alpha-methyl ester beta-dimethylamide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, pyrrolidineamide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, pyrrolidineamide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, morpholineamide;
N-[6[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, N-methylpiperazineamide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, N-methyl-N-[2-(1-morpholinyl)ethyl]amide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, N-methyl-N-[2-(1-piperidinyl)ethyl]amide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-tryptophan, dimethylamino;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-threonine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-serine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylglycine, 1,1-dimethylethyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-3,5-diiodo-O-methyl-L-tyrosine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-4-iodo-L-phenylalanine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-methionine sulfone, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-beta-naphthylalanine, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-2-aminoisobutyric acid, methyl ester:
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-1-cyclopropanecarboxylic acid, methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-[l-(4-cyanophenyl)]-3S-aminopyrrolidin-2-one;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-1,1-benzoxazin-2-yl]-L-alanine, N-methyl-N-allylamide;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-5 oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, N-methyl-N-phenylmethylamide;
N-[6[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, phenyl methyl ester;
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-3,5-diiodo-L-tyrosine, methyl ester;
N-[6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, dimethylamide;
N-[6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, morpholineamide;
N-[6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, pyrrolidineamide;
N-[6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, morpholineamide;
N-[6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, dimethylamide;
N-[6-[[[(1,1-dimethylethoxy)carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
N-[6-amino-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
N-[6-amino-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-1-phenylalanine, methyl ester;
N-[6-aminomethyl-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, pyrrolidineamide;
N-[6-[[[[dimethylaminomethyl]carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, pyrrolidineamide;
N-[6-[[[[(1-pyrrolidinyl)methyl]carbonyl]amino]methyl]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-O-methyl-L-tyrosine, pyrrolidineamide;
N-[[6-(dimethylaminomethyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
5-methyl-N-6-[[(2-pyridyl)carbonyl]amino]-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
N-[6-[[(5-isoxazolyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
N-[6-[[(methoxymethyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
N-[6-[[(methoxymethyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[6-[[(2-carbonylethyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[6-[[(cyclobutyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[N-[[(2-furanyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[6-[[(2-thienylmethyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[6-[[(2-thienylmethyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, morpholineamide;
N-[6-[[(2-thienylmethyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, pyrrolidineamide;
N-[6-[[[[2-(2-thienyl)ethyl]amino]carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[6-[[[[2-(2-thienyl)ethyl]amino]carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
N-[6[[(1-morpholinyl)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester;
N-[6-[benzenesulfonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-phenylalanine, methyl ester;
N-[6-[benzenesulfonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine, methyl ester; and
N-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl]-L-alanine.
The term xe2x80x9chydridoxe2x80x9d denotes a single hydrogen atom (H). This hydrido radical may be attached, for example, to an oxygen atom to form a hydroxyl radical or two hydrido radicals may be attached to a carbon atom to form a methylene (xe2x80x94CH2xe2x80x94) radical. Where used, either alone or within other terms such as xe2x80x9chaloalkylxe2x80x9d, xe2x80x9calkylsulfonylxe2x80x9d, xe2x80x9calkoxyalkylxe2x80x9d, xe2x80x9chydroxyalkylxe2x80x9d and xe2x80x9caralkylxe2x80x9d the term xe2x80x9calkylxe2x80x9d embraces linear or branched radicals having one to about twenty carbon atoms or, preferably, one to about twelve carbon atoms. More preferred alkyl radicals are xe2x80x9clower alkylxe2x80x9d radicals having one to about ten carbon atoms. Most preferred are lower alkyl radicals having one to about six carbon atoms. Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl and the like. The term xe2x80x9calkenylxe2x80x9d embrace linear or branched radicals having at least one carbonxe2x80x94carbon double bond of two to about twenty carbon atoms or, preferably, two to about twelve carbon atoms, provided that the double bond does not occur at the point of attachment of the radical. More preferred alkenyl radicals are xe2x80x9clower alkenylxe2x80x9d radicals having two to about six carbon atoms. Examples of such radicals include ethenyl, n-propenyl, butenyl, and the like. The term xe2x80x9chaloxe2x80x9d means halogens such as fluorine, chlorine, bromine or iodine. The term xe2x80x9chaloalkylxe2x80x9d embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have either an iodo, bromo, chloro or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals may have two or more of the same halo atoms or a combination of different halo radicals. xe2x80x9cLower haloalkylxe2x80x9d embraces radicals having 1-6 carbon atoms. Examples of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. The term xe2x80x9chydroxyalkylxe2x80x9d embraces linear or branched alkyl radicals having one to about ten carbon atoms any one of which may be substituted with one or more hydroxyl radicals. More preferred hydroxyalkyl radicals are xe2x80x9clower hydroxyalkylxe2x80x9d radicals having one to six carbon atoms and one or more hydroxyl radicals. Examples of such radicals include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl. The terms xe2x80x9calkoxyxe2x80x9d and xe2x80x9calkoxyalkylxe2x80x9d embrace linear or branched oxy-containing radicals each having alkyl portions of one to about ten carbon atoms. More preferred alkoxy radicals are xe2x80x9clower alkoxyxe2x80x9d radicals having one to six carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy and tert-butoxy. The term xe2x80x9calkoxyalkylxe2x80x9d, also embraces alkyl radicals having two or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals. More preferred alkoxyalkyl radicals are xe2x80x9clower alkoxyalkylxe2x80x9d radicals having one to six carbon atoms and one or two alkoxy radicals. Examples of such radicals include methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl and methoxypropyl. The xe2x80x9calkoxyxe2x80x9d or xe2x80x9calkoxyalkylxe2x80x9d radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide xe2x80x9chaloalkoxyxe2x80x9d or haloalkoxyalkyl radicals. More preferred haloalkoxy radicals are xe2x80x9clower haloalkoxyxe2x80x9d radicals having one to six carbon atoms and one or more halo radicals. Examples of such radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, trifluoroethoxy, fluoroethoxy and fluoropropoxy. The term xe2x80x9carylxe2x80x9d, alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached together in a pendent manner or may be fused. The term xe2x80x9carylxe2x80x9d embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl. Aryl moieties may also be substituted at a substitutable position with one or more substituents selected independently from alkyl, aralkyl, alkoxyalkyl, alkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl aminocarbonylalkyl, alkoxy, aralkoxy, heterocyclylalkoxy, alkylaminoalkoxy, carboxyamino, carboxyaminoalkyl, carboxyaminoaralkyl, amino, halo, nitro, alkylamino, alkylcarbonylamino, arylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino, alkylsulfonylamino, arylsulfonylamino, acyl, cyano, carboxy, aminocarbonyl, alkoxycarbonyl and aralkoxycarbonyl. The terms xe2x80x9cheterocyclylxe2x80x9d or xe2x80x9cheterocyclicxe2x80x9d embrace saturated, partially saturated and unsaturated heteroatom-containing ring-shaped radicals, where the heteroatoms may be selected from nitrogen, sulfur and oxygen. Examples of saturated heterocyclic radicals include saturated 5 to 7-membered heteromonocylic group containing 1 to 4 nitrogen atoms [e.g. pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, tropanyl, homotropanyl, etc.]; saturated 5 to 7-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. morpholinyl, etc.]; saturated 5 to 7-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., thiazolidinyl, etc.]. Examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran, oxazolinyl, dihydrofuran and dihydrothiazole. Examples of unsaturated heterocyclic radicals, also termed xe2x80x9cheteroarylxe2x80x9d radicals include unsaturated 5 to 7 membered heteromonocyclic group containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl, azepinyl, pyrazinyl, pyridazinyl, triazolyl [e.g., 4H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.] tetrazolyl [e.g 1H-tetrazolyl, 2H-tetrazolyl, etc.], etc.; unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g., tetrazolo [1,5-b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, furyl, etc.; unsaturated 5 to 7-membered heteromonocyclic group containing a sulfur atom, for example, thienyl, etc.; unsaturated 5 to 7-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. benzoxazolyl, benzoxadiazolyl, etc.]; unsaturated 5 to 7-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g., 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., benzothiazolyl, benzothiadiazolyl, etc.] and the like. The term also embraces radicals where heterocyclic radicals are fused with aryl radicals. Examples of such fused bicyclic radicals include benzofuryl, benzothienyl, and the like. Said xe2x80x9cheterocyclylxe2x80x9d radicals may also be substituted at a substitutable position with one or more substituents selected independently from alkyl, aralkyl, alkoxyalkyl, alkylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkoxy, aralkoxy, alkylaminoalkoxy, aminocarboxy, alkylaminocarboxy, aralkylaminocarboxy, amino, halo, nitro, alkylamino, alkylcarbonylamino, arylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, aminocarbonylamino, alkylaminocarbonylamino, alkylsulfonylamino, arylsulfonylamino, acyl, cyano, carboxy, aminocarbonyl, alkoxycarbonyl and aralkoxycarbonyl. More preferred heteroaryl radicals include five to six membered heteroaryl radicals. The term xe2x80x9ccycloalkylxe2x80x9d embraces radicals having three to ten carbon atoms. More preferred cycloalkyl radicals are xe2x80x9clower cycloalkylxe2x80x9d, radicals having three to seven carbon atoms. Examples include radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term xe2x80x9ccycloalkylalkylxe2x80x9d embraces cycloalkyl radicals as defined above attached to alkyl radicals of one to ten carbon atoms. More preferred cycloalkylalkyl radicals are xe2x80x9clower cycloalkylalkylxe2x80x9d radicals having alkyl radicals of one to six carbon atoms. Examples include radicals such as cyclopropylpropyl, cyclobutylethyl cyclopentylmethyl, and cyclohexylmethyl. The term xe2x80x9cmercaptoalkylxe2x80x9d, embraces radicals containing a free xe2x80x94SH group attached to an linear or branched alkyl radical, as defined above. Examples of such mercaptoalkyl radicals are mercatomethyl, mercaptopropyl and mercaptohexyl. The term xe2x80x9calkylthioxe2x80x9d embraces radicals containing a linear or branched alkyl radical, of one to about ten carbon atoms attached to a divalent sulfur atom. More preferred alkylthio radicals are xe2x80x9clower alkylthioxe2x80x9d radicals having alkyl radicals of one to six carbon atoms. Examples of such lower alkylthio radicals are methylthio, ethylthio, propylthio, butylthio and hexylthio. The term xe2x80x9calkylthioalkylxe2x80x9d, embraces alkylthio radicals attached to an alkyl radical. More preferred alkylthioalkyl radicals are xe2x80x9clower alkylthioalkylxe2x80x9d, radicals having alkyl radicals of one to six carbon atoms and an alkylthio radical as described above. Examples of such radicals include methylthiomethyl. The term xe2x80x9calkylsulfinylxe2x80x9d embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, attached to a divalent xe2x80x94S(xe2x95x90O)xe2x80x94 radical. More preferred alkylsulfinyl radicals are xe2x80x9clower alkylsulfinylxe2x80x9d radicals having one to six carbon atoms. Examples of such lower alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, butylsulfinyl and hexylsulfinyl. The term xe2x80x9csulfonylxe2x80x9d, whether used alone or linked to other terms such as alkylsulfonyl, denotes respectively divalent radicals xe2x80x94SO2xe2x80x94. xe2x80x9cAlkylsulfonylxe2x80x9d embraces alkyl radicals attached to a sulfonyl radical, where alkyl is defined as above. More preferred alkylsulfonyl radicals are xe2x80x9clower alkylsulfonylxe2x80x9d radicals having one to six carbon atoms. Examples of such lower alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl and propylsulfonyl. The xe2x80x9calkylsulfonylxe2x80x9d radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide xe2x80x9chaloalkylsulfonylxe2x80x9d, radicals. More preferred haloalkylsulfonyl radicals are xe2x80x9clower haloalkylsulfonylxe2x80x9d radicals having one or more halo atoms attached to lower alkylsulfonyl radicals as described above. Examples of such lower haloalkylsulfonyl radicals include fluoromethylsulfonyl, trifluoromethylsulfonyl and chloromethylsulfonyl. The term xe2x80x9carylsulfonylxe2x80x9d embraces aryl radicals as defined above, attached to a sulfonyl radical. Examples of such radicals include phenylsulfonyl. The terms xe2x80x9csulfamylxe2x80x9d, xe2x80x9caminosulfonylxe2x80x9d and xe2x80x9csulfonamidylxe2x80x9d denotes NH2O2Sxe2x80x94. The term xe2x80x9cacylxe2x80x9d denotes a radical provided by the residue after removal of hydroxyl from an organic acid. Examples of such acyl radicals include formyl, alkanoyl and aroyl radicals. The term xe2x80x9calkylsulfinylalkylxe2x80x9d, embraces radicals containing an alkylsulfinyl radical, as described above, attached to an alkyl radical. More preferred alkylsulfinylalkyl radicals are xe2x80x9clower alkylsulfinylalkylxe2x80x9d radicals having one to six carbon atoms. Examples of such lower alkylsulfinylalkyl radicals include methylsulfinylethyl, ethylsulfinylmethyl, butylsulfinylethyl and methylsulfinylmethyl. xe2x80x9cAlkylsulfonylalkylxe2x80x9d embraces alkylsulfonyl radicals attached to an alkyl radical, where alkyl and alkylsulfonyl are defined above. More preferred alkylsulfonylalkyl radicals are xe2x80x9clower alkylsulfonylalkylxe2x80x9d radicals having one to six carbon atoms. Examples of such lower alkylsulfonylalkyl radicals include methylsulfonylmethyl, ethylsulfonylethyl and methylsulfonylethyl. The terms xe2x80x9ccarboxyxe2x80x9d or xe2x80x9ccarboxylxe2x80x9d, whether used alone or with other terms;, such as xe2x80x9ccarboxyalkylxe2x80x9d, denotes xe2x80x94CO2H. The term xe2x80x9ccarbonylxe2x80x9d, whether used alone or with other terms, such as xe2x80x9calkoxycarbonylxe2x80x9d, denotes xe2x80x94(Cxe2x95x90O)xe2x80x94. The term xe2x80x9calkoxycarbonylxe2x80x9d means a radical containing an alkoxy radical, am defined above, attached via an oxygen atom to a carbonyl radical. Preferably, xe2x80x9clower alkoxycarbonylxe2x80x9d embraces alkoxy radicals having one to six carbon atoms. Examples of such xe2x80x9clower alkoxycarbonylxe2x80x9d ester radicals include substituted or unsubstituted methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl and hexyloxycarbonyl. The term xe2x80x9caralkylxe2x80x9d embraces aryl-substituted alkyl radicals. Preferable aralkyl radicals are xe2x80x9clower aralkylxe2x80x9d radicals having aryl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such radicals include benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylethyl. The aryl in said aralkyl may be additionally substituted as described above. The term xe2x80x9caralkenylxe2x80x9d, embraces aryl-substituted alkenyl radicals. Preferable aralkenyl radicals are xe2x80x9clower phenylalkenylxe2x80x9d radicals having phenyl radicals attached to alkenyl radicals having one to six carbon atoms. Examples of such radicals include phenylethenyl and phenylpropenyl. The aryl in said aralkyl may be additionally substituted as described above. The terms benzyl and phenylmethyl are interchangeable. The term xe2x80x9calkylcarbonylxe2x80x9d includes radicals having alkyl radicals as defined above, attached to a carbonyl radical. More preferred alkylcarbonyl radicals are xe2x80x9clower alkylcarbonylxe2x80x9d radicals having one to six carbon atoms. Examples of such radicals include methylcarbonyl and ethylcarbonyl. The term xe2x80x9calkoxycarbonylalkylxe2x80x9d, embraces radicals having xe2x80x9calkoxycarbonylxe2x80x9d, as defined above substituted to an alkyl radical. More preferred alkoxycarbonylalkyl radicals are xe2x80x9clower alkoxycarbonylalkylxe2x80x9d having lower alkoxycarbonyl radicals as defined above attached to one to six carbon atoms. Examples of such lower alkoxycarbonylalkyl radicals include methoxycarbonylmethyl. The term xe2x80x9chaloalkylcarbonylxe2x80x9d embraces radicals having a haloalkyl radical as described above attached to a carbonyl radical. More preferred radicals are xe2x80x9clower haloalkylcarbonylxe2x80x9d radicals where lower haloalkyl radicals, as described above are attached to a carbonyl radical. The term xe2x80x9ccarboxyalkylxe2x80x9d, embraces radicals having a carboxy radical as defined above, attached to an alkyl radical. The alkanoyl radicals may be substituted or unsubstituted, such as formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, trifluoroacetyl or the like, in which the preferable one is formyl, acetyl, propionyl or trifluoroacetyl. The term xe2x80x9cheterocyclylalkylxe2x80x9d embraces heterocyclic-substituted alkyl radicals. More preferred heterocyclylalkyl radicals are xe2x80x9clower heterocyclylalkylxe2x80x9d radicals having five to six membered heterocyclyl radicals attached to lower alkyl radicals having one to six carbon atoms. Examples of such radicals include pyrrolidinylmethyl, piperidinylmethyl, morpholinylmethyl, piperazinylmethyl, oxazolylmethyl, oxazolylethyl, oxazolinylmethyl, oxazolinylethyl, indolylethyl, indolylmethyl, pyridylmethyl, quinolylmethyl, thienylmethyl, furylethyl and quinolylethyl. The heterocyclic in said heterocyclylalkyl may be additionally substituted as described above. The term xe2x80x9caryloxylxe2x80x9d embraces aryl radicals, as defined above, attached to an oxygen atom. The aryl in said aryloxy may be additionally substituted as described above. Examples of such radicals include phenoxy. The term xe2x80x9caralkoxyxe2x80x9d embraces oxy-containing aralkyl radicals attached through an oxygen atom to other radicals. The term xe2x80x9caralkoxyalkylxe2x80x9d, embraces alkyl radicals having one or more aralkoxy radicals attached to the alkyl radical, that is, to form monoaralkyloxyalkyl and diaralkyloxyalkyl radicals. The xe2x80x9caralkoxyxe2x80x9d or xe2x80x9caralkoxyalkylxe2x80x9d radicals may be further substituted on the aryl ring portion of the radical. More preferred aralkoxyalkyl radicals are xe2x80x9clower aralkoxyalkylxe2x80x9d having an alkoxy attached to one to six carbon atoms. Examples of lower aralkoxyalkyl radicals include benzyloxymethyl. The term xe2x80x9caminoalkylxe2x80x9d embraces alkyl radicals substituted with amino radicals. More preferred aminoalkyl radicals are xe2x80x9clower aminoalkylxe2x80x9d having one to six carbon atoms. Examples include aminomethyl, aminoethyl and aminobutyl. The term xe2x80x9cquanidinoalkylxe2x80x9d denotes a guanidino radical [xe2x80x94Cxe2x95x90NH2(NH2)2] attached to an alkyl radical as defined above. More preferred alkylamino radicals are xe2x80x9clower alkylaminoxe2x80x9d radicals having one or two alkyl radicals of one to six carbon atoms, attached to a nitrogen atom. The term xe2x80x9calkylaminoxe2x80x9d denotes amino groups which have been substituted with one or two alkyl radicals. More preferred alkylamino radicals are xe2x80x9clower alkylaminoxe2x80x9d having alkyl radicals of one to six carbon atoms attached to the nitrogen atom of an amine. Suitable xe2x80x9clower alkylaminoxe2x80x9d may be mono or dialkylamino such as N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino or the like. The term xe2x80x9calkylaminoalkylxe2x80x9d, denotes alkylamino groups, as defined above, attached to an alkyl radical. More preferred alkylaminoalkyl radicals are xe2x80x9clower alkylaminoalkylxe2x80x9d having one to six carbon atoms attached to a lower aminoalkyl radical as described above. Suitable xe2x80x9clower alkylaminoalkylxe2x80x9d, may be mono or dialkylaminoalkyl radicals such as N-methylaminomethyl, N-ethylaminomethyl, N,N-dimethylaminomethyl, N,N-dimethylaminoethyl N,N-dimethylaminopropyl or the like. The term xe2x80x9cdialkylaminoalkylxe2x80x9d, also includes radicals where the bridging alkyl moiety is optionally substituted with alkylsulfonyl, alkoxy, aralkoxy, heterocyclyl, and aryl. The term xe2x80x9calkylaminoalkoxyxe2x80x9d denotes alkylamino groups, as defined above, attached to an alkoxy radical. Suitable xe2x80x9calkylaminoalkoxyxe2x80x9d may be mono or dialkylaminoalkoxy radicals such as N-methylaminomethoxy, N-ethylaminomethoxy, N,N-dimethylaminomethoxy, N,N-dimethylaminoethoxy N,N-dimethylaminopropoxy or the like. The term xe2x80x9calkylaminocarbonylxe2x80x9d embraces alkylamino radicals, as described above, to a carbonyl radical. More preferred alkylaminocarbonyl radicals are xe2x80x9clower alkylaminocarbonylxe2x80x9d having lower alkylamino radicals, as described above, attached to a carbonyl radical. Examples. of such radicals include N-methylaminocarbonyl and N,N-dimethylcarbonyl. The term xe2x80x9carylaminoxe2x80x9d denotes amino groups which have been substituted with one or two aryl radicals, such as N-phenylamino. The xe2x80x9carylaminoxe2x80x9d radicals may be further substituted on the aryl ring portion of the radical. The terms xe2x80x9cN-arylaminoalkylxe2x80x9d and xe2x80x9cN-aryl-N-alkylaminoalkylxe2x80x9d denote amino groups which have been substituted with one aryl radical or one aryl and one alkyl radical, respectively, and having the amino group attached to an alkyl radical. More preferred arylaminoalkyl radicals are xe2x80x9clower arylaminoalkylxe2x80x9d having the arylamino radical attached to one to six carbon atoms. Examples of such radicals include N-phenylaminomethyl and N-phenyl-N-methylaminomethyl. The term xe2x80x9caminocarbonylxe2x80x9d denotes an amide group of the formula xe2x80x94C(xe2x95x90O)NH2. The term xe2x80x9caminocarbonylalkylxe2x80x9d denotes an aminocarbonyl group attached to an alkyl radical. More preferred are xe2x80x9clower aminocarbonylalkylxe2x80x9d having lower aminocarbonyl radicals as described above attached to alkyl of one to six carbon atoms. The term xe2x80x9calkylaminocarbonylalkylxe2x80x9d denotes an aminocarbonyl group which has been substituted with one or two alkyl radicals and attached to an alkyl radical. More preferred are xe2x80x9clower alkylaminocarbonylalkylxe2x80x9d having lower alkylaminocarbonyl radicals as described above attached to alkyl radicals of one to six carbon atoms. The term xe2x80x9caryloxyalkylxe2x80x9d embraces alkyl radicals having one or more aryloxy radicals, aryl radicals attached to a divalent oxygen atom, attached to the alkyl radical, that is, to form monoaryloxyalkyl and diaryloxyalkyl radicals. The more preferred aryloxyalkyl radicals are xe2x80x9clower aryloxyalkylxe2x80x9d radicals having aryloxy radicals attached to one to six carbon atoms. Examples include phenoxymethyl. xe2x80x9cAmino acid residuexe2x80x9d means any of the naturally occurring alpha-, beta- and gamma-amino carboxylic acids, including their D and L optical isomers and racemic mixtures thereof, synthetic amino acids, and derivatives of these natural and synthetic amino acids. The amino acid residue is bonded through a nitrogen of the amino acid. The naturally occurring amino acids which can be incorporated in the present invention include, but are not limited to, alanine, arginine, asparagine, aspartic acid, cysteine, cystine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, thyroxin, tryptophan, tyrosine, valine, xcex2-alanine, and xcex3-aminobutyric acid. Derivatives of amino acids which can be incorporated in the present invention include, but are not limited to amino acids having protected and modified carboxylic acids, including acid esters and amides, protected amines, and substituted phenyl rings, including but not limited to alkyl, alkoxy and halo substituted tyrosine and phenylalanine.
The present invention comprises a pharmaceutical composition comprising a therapeutically-effective amount of a compound of Formulas I-II in association with at least one pharmaceutically-acceptable carrier, adjuvant or diluent.
The present invention also comprises a method of therapeutic and prophylactic treatment of viral infections, particularly herpetoviridae infection, in a subject, the method comprising treating the subject having such herpes infection a therapeutically-effective amount of a compound of Formulas I-II.
The present invention also comprises a method of inhibiting a viral protease, the method comprising administering a therapeutically-effective amount of a compound of Formulas I-II.
Also included in the family of compounds of Formula I are the stereoisomers and tautomers thereof. Compounds of the present invention can possess one or more asymmetric carbon atoms and are thus capable of existing in the form of optical isomers as well as in the form of racemic or non-racemic mixtures thereof. Accordingly, some of the compounds of this invention may be present in racemic mixtures which are also included in this invention. The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processes, for example by formation of diastereoisomeric salts by treatment with an optically active acid or base. Examples of appropriate acids are tartaric, diacetyltartaric, dibenzoyltartaric, ditoluoyltartaric and camphorsulfonic acid and then separation of the mixture of diastereoisomers by crystallization followed by liberation of the optically active bases from these salts. A different process for separation of optical isomers involves the use of a chiral chromatography column optimally chosen to maximize the separation of the enantiomers. Still another available method involves synthesis of covalent diastereoisomeric molecules by reacting an amine functionality of precursors to compounds of Formula I with an optically pure acid in an activated form or an optically pure isocyanate. Alternatively, diastereomeric derivatives can be prepared by reacting a carboxyl functionality of precursors to compounds of Formula I with an optically pure amine base. The synthesized diastereoisomers can be separated by conventional means such as chromatography, distillation, crystallization or sublimation, and then hydrolyzed to deliver the enantiomerically pure compound. The optically active compounds of Formula I can likewise be obtained by utilizing optically active starting materials. These isomers may be in the form of a free acid, a free base, an ester or a salt. Additional methods for resolving optical isomers, known to those skilled in the art may be used, for example, those discussed by J. Jaques et al in Enantiomers, Racemates, and Resolutions, John Wiley and Sons, New York (1981).
Also included in the family of compounds of Formula I are the pharmaceutically-acceptable salts thereof. The term xe2x80x9cpharmaceutically-acceptable saltsxe2x80x9d embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically-acceptable. Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula I may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, example of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, plenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethylsulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic, stearic, cyclohexylaminosulfonic, algenic, xcex2-hydroxybutyric, galactaric and galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of Formula I include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,Nxe2x80x2-dibenzylethylenediamine, choline, chloroprocaine, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these salts may be prepared by conventional means from the corresponding compound of Formula I by reacting, for example, the appropriate acid or base with the compound of Formula I.